Category: Statistics

Turk Neurosurg. 2024 Jan 11. doi: 10.5137/1019-5149.JTN.43568-23.2. Online ahead of print.

ABSTRACT

AIM: This study aims to assess the clinicopathological and prognostic significance of Tim-3, an immune checkpoint molecule, and Rel-B, an NF-κB subunit, in grade 4 diffuse glioma samples and their relationship with each other.

MATERIAL AND METHODS: The demographic, radiologic, prognostic, and treatment data of patients diagnosed with grade 4 diffuse glioma between 2016 and 2019 were reviewed and recorded. Tim-3 and Rel-B were applied to the paraffin-embedded tissues by immunohistochemistry method. Tim-3 expression was grouped as immunoreactivity density score (IDS) (Low, High) and expression percentage ( 12%, 12%), while Rel-B expression was divided into positive and negative groups.

RESULTS: 99 grade 4 diffuse glioma samples were detected, 8 of which were IDH-1 positive. Tim-3 was expressed only in immune cells around and inside the tumoral tissue, and expression was detected only in tumoral cells with Rel-B. Tim-3 IDS was found at lower levels (median 31.8) in IDH-1 positive cases and higher (median 158) in IDH-1 negative ones (p=0.020). A significant correlation was found between the Tim-3 IDS high group and Rel-B positivity (p=0.007). In the IDH-1 negative cohort, the univariate analysis revealed higher Tim-3 expression percentage and higher IDS were associated with better overall survival (OS) (p=0.041 and p=0.042 respectively) and progression-free survival (PFS) (p=0.023 and p=0.029 respectively), while in the multivariate analysis higher Tim-3 expression percentage was found to be an independent predictor for better OS (p=0.008) and PFS (p=0.022). Rel-B positive cases exhibited longer OS and PFS but the result was not statistically significant (p 0.05).

CONCLUSION: Tim-3 can be a good prognostic predictor and treatment candidate, especially in patients with IDH-1 negative grade 4 diffuse gliomas however, further studies with more cases are needed for Rel-B. The significant relationship between Tim-3 and Rel-B expressions supported the interaction between NF-κB and immune checkpoint pathways.

PMID:39840558 | DOI:10.5137/1019-5149.JTN.43568-23.2

BJU Int. 2025 Jan 22. doi: 10.1111/bju.16641. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the association between prostate-specific antigen (PSA) density (PSAD) and prostate cancer mortality after a benign result on systematic transrectal ultrasonography (TRUS)-guided prostate biopsy.

PATIENTS AND METHODS: This retrospective study used data from the Finnish Randomised Study of Screening for Prostate Cancer (FinRSPC) collected between 1996 and 2020. We identified men aged 55-71 years randomised to the screening arm with PSA ≥4.0 ng/mL and a benign systematic TRUS-guided biopsy result. The cumulative prostate cancer mortality of men stratified by a PSAD cutoff of 0.15 ng/mL/cm³ was modelled with competing risk functions. The ability of PSAD, PSA, and base variables (age at biopsy, DRE result, socioeconomic status, 5α-reductase inhibitor usage, family history, and Charlson Comorbidity Index (CCI)) to predict prostate cancer death was compared using c-statistics and a likelihood ratio test.

RESULTS: After excluding 10 men without PSA data within 2 years of the biopsy and 65 without prostate volume data, 2276 men were eligible for inclusion in the study. A total of 50 men died from prostate cancer and 1028 from other causes during a median (interquartile range) follow-up of 17.4 (13.2-20.9) years. The cumulative prostate cancer mortality of men with PSAD <0.15 ng/mL/cm³ was significantly lower than that of men with PSAD ≥0.15 ng/mL/cm³: 0.5% (95% confidence interval [CI] 0.2%-1.1%) vs 2.0% (95% CI 1.2%-3.1%) at 15 years (Grey’s test, P = 0.001). The model consisting of PSAD, PSA and the base variables predicted prostate cancer mortality (c-statistic 0.781) significantly better than either the base variables alone (c-statistic 0.737; likelihood-ratio test, P = 0.003) or the base variables and PSA (c-statistic 0.765; likelihood-ratio test, P = 0.039).

CONCLUSION: Prostate cancer mortality after a benign systematic TRUS-guided biopsy is low. In these patients, PSAD predicts prostate cancer mortality and provides additional value to other clinical variables. PSAD-based stratification can be used to guide follow-up strategy.

PMID:39840544 | DOI:10.1111/bju.16641

J Clin Pharmacol. 2025 Jan 22. doi: 10.1002/jcph.6192. Online ahead of print.

ABSTRACT

Obesity significantly influences drug pharmacokinetics (PK), which challenges optimal dosing. This study examines the effects of diet-and-exercise-induced weight loss on key drug-metabolizing enzymes and gastric emptying in patients with obesity, who frequently require medications for comorbidities. Participants followed a structured weight management program promoting weight loss over 3-6 months and were not concomitantly on potential CYP inducers or inhibitors. Using a drug cocktail of acetaminophen, caffeine, omeprazole, and midazolam, we assessed UGT1A1, CYP1A2, CYP2C19, and CYP3A4 enzyme activities before and after weight loss, respectively, by measuring parent and metabolite concentrations. The time to maximum acetaminophen plasma concentrations reflected the gastric emptying time. PK profiles were compared across two phases: baseline (Phase 1) and post-weight loss (Phase 2). Twenty-four participants enrolled, 21 completed Phase 1 and 12 completed both phases. Statistically significant (N = 12, P < .05) gains in CYP2C19 and CYP3A4 activity were observed after weight loss of 7.6% to 26.2%, with a median [25th, 75th percentile] increase in activity of 90.5 [15.0, 194.3] % and 43.0 [7.5, 68.0] %, respectively. A 2- or 3-h single plasma sample-based ratio of the metabolite to parent concentration strongly correlated with the respective AUC ratio for the drug metabolism phenotype (N = 21). Our findings provide provisional data for evaluation of the effects of non-pharmacologically and non-surgically induced weight loss on gastric emptying and drug metabolism for future physiologically based PK models. Development of mechanistic models to optimize drug dosing in obesity are necessary since weight and body composition shifts are expected with emerging new treatments.

PMID:39840538 | DOI:10.1002/jcph.6192

J Endovasc Ther. 2025 Jan 22:15266028241312356. doi: 10.1177/15266028241312356. Online ahead of print.

ABSTRACT

OBJECTIVE: There is a lack of consensus regarding the optimal antithrombotic therapy (ATT) after popliteal and infrapopliteal (PIP) endovascular therapy (EVT). Currently, dual antiplatelet therapy (DAPT) for 3 months and single antiplatelet therapy (SAPT) are the most prescribed regimens in the Netherlands. Thus far, no randomized comparison has been performed on the optimal ATT approach. Therefore, this study compared the efficacy and safety of 3-month DAPT with SAPT following PIP EVT.

DESIGN: Retrospective analysis of prospectively collected data from a multicenter registry.

METHODS: The Dutch chronic lower limb-threatening ischemia registry (THRILLER) collected prospective data on patients enrolled between January 2021 and October 2023. As for ATT, only patients prescribed antiplatelet therapy (APT), were included in this analysis. The primary efficacy outcome was a composite of 3-month major adverse cardiovascular events (MACEs, ie, myocardial infarction, cerebrovascular event, cardiovascular death), major adverse limb events (MALEs, ie, major amputation, reintervention), and non-cardiovascular death. Secondary efficacy outcomes were 3-month MACE, MALE, and all-cause mortality. The primary safety outcome was major bleeding according to the ‘Thrombolysis In Myocardial Infarction’ (TIMI) classification. Descriptive statistics and Cox proportional hazard models were applied.

RESULTS: In total, 460 of 840 THRILLER patients used DAPT or SAPT as ATT and were therefore included in the analysis. Of these, 322 (70%) received DAPT and 138 (30%) received SAPT. In total, 73 (15.9%) primary efficacy outcomes were observed of which 21 (15.2%) events in the SAPT group and 52 (16.1%) events in the DAPT group. No significant differences were observed between SAPT and DAPT for the primary efficacy outcomes or any of the secondary efficacy outcomes. In both groups, one case of major bleeding was observed.

CONCLUSION: The findings suggest that 3 months of DAPT is not superior to SAPT. A well-powered randomized trial is warranted to assess the efficacy and safety of post-procedural DAPT in chronic limb-threatening ischemia (CLTI) patients undergoing PIP EVT.

CLINICAL IMPACT: This manuscript reports on the efficacy and safety outcomes of 3 months of DAPT versus SAPT, which are commonly chosen therapies following popliteal and infrapopliteal endovascular therapy. No significant difference was found between the two groups regarding major adverse cardiovascular events, all-cause death, major amputation, or major bleeding. Therefore, 3 months of DAPT does not seem superior to SAPT. These results suggest that SAPT appears to be a sufficient alternative when considering 3 months of DAPT. Further research should verify these outcomes and focus on the efficacy and safety of prolonged DAPT suppletion after endovascular therapy.

PMID:39840536 | DOI:10.1177/15266028241312356

J Clin Pharmacol. 2025 Jan 22. doi: 10.1002/jcph.6191. Online ahead of print.

ABSTRACT

Albuvirtide (ABT) is a novel long-acting fusion inhibitor for human immunodeficiency virus type 1 (HIV-1), and may be co-administered with rifampicin (RIF) in patients concurrent with tubercle bacillus and HIV-1. This study was conducted to investigate the pharmacokinetic effect of co-administration of the two drugs. In the study, 24 healthy volunteers were randomized to receive ABT alone or with RIF. Plasma concentrations were measured using liquid chromatography-tandem mass spectrometry for RIF and competitive enzyme-linked immunosorbent assay for ABT. Co-administration with RIF increased the maximum concentration (C_max) of ABT by 6.93%, and the area under the plasma concentration-time curve (AUC) from time 0 to the last quantifiable concentration (AUC_0-t) by 21.31%; the geometric mean ratio values (GMRs) for C_max and AUC_0-t of ABT when co-administered with RIF, relative to administered alone, were 106.93% (90% confidence interval [CI] 97.53%-117.23%) and 121.31% (90% CI 108.68%-135.40%), respectively. Co-administration with ABT decreased the steady-state C_max (C_max,ss) of RIF by 10.19%, and the steady-state AUC from time 0 to 24 h (AUC_{0-24 h,ss}) by 19.93%; the GMRs for C_max,ss and AUC_{0-24 h,ss} of RIF when co-administered with ABT, relative to administered alone, were 89.81% (90% CI, 79.97%-104.79%) and 80.07% (90% CI 75.68%-84.72%), respectively. The time to reach Cmax (Tmax) of both ABT and RIF demonstrated no statistically significant difference, whether administered alone or concurrently. The pharmacokinetics profiles of both RIF and ABT changed to some extent when co-administered, while no clinically significant impact on these two drugs was observed, indicating that ABT and RIF can be used together without necessitating dose adjustments.

PMID:39840531 | DOI:10.1002/jcph.6191

J Anat. 2025 Jan 22. doi: 10.1111/joa.14195. Online ahead of print.

ABSTRACT

The fibula, despite being traditionally overlooked compared to the femur and the tibia, has recently received attention in primate functional morphology due to its correlation with the degree of arboreality (DOA). Highlighting further fibular features that are associated with arboreal habits would be key to improving palaeobiological inferences in fossil specimens. Here we present the first investigation on the trabecular bone structure of the primate fibula, focusing on the distal epiphysis, across a vast array of species. We collected μCT data on the distal fibula for 21 species of primates, with representatives from most of the orders, and we employed a recently developed approach implemented in the R package ‘indianaBones’ to isolate the entire trabecular bone underlying an epiphysis or articular facet. After extracting both traditional trabecular parameters and novel topological indices, we tested for the posited relationship between trabecular bone and DOA. To disentangle this effect from others related to body size and phylogenetic relationship, we included a body mass proxy as covariate and employed phylogenetic comparative methods. We ran univariate/multivariate and exploratory/inferential statistical analyses. The trabecular structure of the fibular distal epiphysis in primates does not appear to be associated with the DOA. Instead, it is strongly affected by body mass and phylogenetic relationships. Although we identified some minor trends related to human bipedalism, our findings overall discourage, at this stage, the study of distal fibula trabecular bone to infer arboreal behaviors in extinct primates. We further found that body size distribution is strongly related to phylogeny, an issue preventing us from unravelling the influence of the two factors and that we believe can potentially affect future comparative analyses of primates. Overall, our results add to previous evidence of how trabecular traits show variable correlation with locomotor aspects, size and phylogenetic history across the primate skeleton, thus outlining a complex scenario in which a network of interconnected factors affects the morphological evolution of primates. This work may represent a starting point for future studies, for example, focusing on the effect of human bipedalism on distal fibula trabecular bone, or aiming to better understand the effects of body size and phylogenetic history on primate morphological evolution.

PMID:39840527 | DOI:10.1111/joa.14195

Sci Prog. 2025 Jan-Mar;108(1):368504241307719. doi: 10.1177/00368504241307719.

ABSTRACT

BACKGROUND: Retail involves directly delivering goods and services to end consumers. Natural disasters and epidemics/pandemics have significant potential to disrupt supply chains, leading to shortages, forecasting errors, price increases, and substantial financial strains on retailers. The COVID-19 pandemic highlighted the need for retail sectors to prepare for crisis impacts on sales forecasts by regularly assessing and adjusting sales volumes, consumer behavior, and forecasting models to adapt to changing conditions.

METHODS: This study explores strategies for adapting sales forecasts and retail approaches in response to such crises. By employing different machine learning (ML) methods, we analyze consumer behavior changes and sales impacts across various product categories, including bottom wear, top wear, one piece, accessories, outwear, and shoes during the COVID-19 pandemic.

RESULTS: The gradient boosting and CatBoost algorithms excelled in product groups with significant sales changes during the pandemic. The Multi-Layer Perceptron (MLP) algorithm performed well in low-volume categories like accessories and footwear. Meanwhile, MLP, LightGBM, and XGBoost were effective in medium-volume categories such as outerwear and underwear.

CONCLUSION: The findings highlight the efficacy of these models in adapting sales forecasts to crisis conditions, offering a practical approach to enhancing retail resilience against future disruptions. This study offers an effective approach for adapting sales forecasting to shifting consumer behaviors during crises.

PMID:39840498 | DOI:10.1177/00368504241307719

Sci Prog. 2025 Jan-Mar;108(1):368504241301520. doi: 10.1177/00368504241301520.

ABSTRACT

PURPOSE: The aim of this study was to evaluate the efficacy and safety of the Ahmed glaucoma valve in pediatric patients with refractory glaucoma.

METHODS: A comprehensive literature search was conducted across multiple major databases, including PubMed, Embase, the Cochrane Library of Systematic Reviews, Science Direct, China’s National Knowledge Infrastructure, and the Wanfang database. We retrieved studies published before December 2022 that met the inclusion criteria, including clinical controlled trials (randomized controlled trials) and clinical noncontrolled trials (non-randomized controlled trials) on the use of Ahmed glaucoma valve in pediatric patients with refractory glaucoma. We performed a meta-analysis and systematic review. The efficacy measures included intraocular pressure, number of anti-glaucoma medications, visual acuity, and success rate. The safety measures were complications. Statistical analysis was performed using RevMan 5.0 software.

RESULTS: We identified 46 eligible studies: Compared with geographic location and study type, the Ahmed glaucoma valve showed a decrease in postoperative intraocular pressure and number of anti-glaucoma medications compared to preoperative levels in children with refractory glaucoma (P < 0.001). Compared with etiological, the Ahmed glaucoma valve showed a decrease in intraocular pressure after surgery compared to preoperative levels in children with refractory glaucoma (SMD: 14.57, 95% CI: 14.05-15.08, P < 0.00 1), and a decrease in postoperative number of anti-glaucoma medications compared to preoperative number of anti-glaucoma medications (SMD: 1.45, 95% CI: 1.37-1.54, P < 0.001). Compared with trabeculectomy revision surgery, there was no significant difference in the complete success rate between the two groups (SMD: 0.86, 95% CI: 0.52-1.39; P = 0.37).Overall, the postoperative intraocular pressure at the time of Ahmed glaucoma valve implantation was lower than that at the time of trabeculectomy revision surgery (SMD: 1.01, 95% CI: 0.71-1.31, I² = 99%, P < 0.001). Subgroup analyses based on whether mitomycin C was use d or not. There was a statistically significant difference in intraocular pressure between Ahmed’s glaucoma valve surgery and preoperative (SMD: 14.13, 95% CI: 13.47-14.80, P = 0.007). Comparison of cumulative complete success rates of Ahmed S2, S3, and Ahmed FP7, FP8 in Ahmed glaucoma valve surgery (SMD: 0.74, 95% CI: 0.38-1.45, I² = 85%, P = 0.38). There is no statistical difference between the two groups. Choroidal effusion and anterior chamber hemorrhage are the two most common adverse events after Ahmed’s glaucoma valve surgery.

CONCLUSIONS: The Ahmed glaucoma valve implantation has some effectiveness in reducing intraocular pressure in children with refractory glaucoma, but there are still many complications. Valve model may not be the key factor affecting the postoperative effectiveness and adverse reactions of refractory glaucoma in children.

PMID:39840485 | DOI:10.1177/00368504241301520

Public Health Nurs. 2025 Jan 22. doi: 10.1111/phn.13539. Online ahead of print.

ABSTRACT

BACKGROUND: Grasping the nuanced needs of older adults is paramount for the efficacious provision of day-care services. Our study sought to identify the demand patterns for day-care services in China and to explore the underlying factors. This study aims to offer useful evidence that can refine nursing care strategies and guide policy development within day-care settings.

METHODS: We implemented a comprehensive electronic survey comprising 46 questions targeting older adults across nine day-care centers in Nanjing, China. Employing latent profile analysis (LPA), we systematically examined and categorized the demand characteristics for day-care services. This analysis was conducted using Mplus version 8.3 and SPSS version 26.0 software, ensuring a rigorous and precise methodological approach.

RESULTS: Our study involved a comprehensive survey of 1016 older adults. The participants were categorized into three groups based on their demand for day-care services: high demand (n = 127), medium demand (n = 197), and low demand (n = 692). The low-demand group exhibited higher levels of social support and better activities of daily living (ADL) scores compared to their counterparts. Multivariate regression analysis indicated that older adults characterized by male gender, advanced age, higher levels of education, receipt of support from a child, presence of chronic diseases, and lower social support and ADL scores exhibited a statistically significant inclination towards moderate to high demand for day-care services (p < 0.05).

CONCLUSION: The demand for day-care services for older adults in China is intricately influenced by a complex array of interrelated factors. Tailoring service offerings to meet the varied physical and emotional needs of older adults is essential, with a particular focus on health and wellness management in day-care centers.

PMID:39840478 | DOI:10.1111/phn.13539

Spine (Phila Pa 1976). 2025 Jan 22. doi: 10.1097/BRS.0000000000005257. Online ahead of print.

ABSTRACT

STUDY DESIGN: A retrospective cohort study.

OBJECTIVE: To determine if there is a difference in reoperations for adjacent segment disease (operative ASD) and nonunion (operative nonunion) in lumbar fusions that stop at T10/T11/T12 versus L1.

SUMMARY OF BACKGROUND DATA: Current lumbar spine surgery is based on the belief that ASD occurs if fusions are stopped at L1 although there is varying evidence to support this assumption.

METHODS: We conducted a cohort study using data from a US-based integrated healthcare system’s Spine Registry of adult patients ≥18 years old with degenerative disc disease/adult lumbar deformity who underwent primary lumbar fusions. The exposure of interest was lumbar fusions stopping at L1 versus T10/T11/T12. Propensity score-weighted Cox proportional hazards regressions were used to evaluate reoperation risk for ASD and for nonunion.

RESULTS: The study cohort included 227 lumbar fusions that stop at L1 and 228 stop at T10/T11/12. Mean age for the cohort was 68.4 years with mean follow-up time of 6.3 years. For caudal level at L5 and S1, we found no statistical differences between operative ASD stopping at L1 versus T10/11/12 (HR=1.03, 95% CI=0.53-2.02, P=0.93 and HR=0.67, 95% CI=0.27-1.67, P=0.39, respectively). For the Short-segment fusions (caudal level: L3,4,5) and Long-segment fusions (L5, S1. S1+ilium) we also found no statistical difference in operative ASD (HR=1.44, 95% CI=0.68-3.09, P=0.34 and HR=0.83, 95% CI=0.52-1.30, P=0.41, respectively). For Long-segment fusions we also found no statistical difference in operative nonunion (HR=0.65, 95% CI=0.20-2.11, P=0.47).

CONCLUSION: Our study provides some evidence against crossing the thoracolumbar junction (TLJ) for individual constructs terminating at S1, as well as for Long-segment fusions, based on comparisons of operative ASD and operative nonunion. However, further research is needed to determine whether this finding holds true for individual constructs with caudal levels at L2, L3, L4, and S1+ilium.

PMID:39840471 | DOI:10.1097/BRS.0000000000005257